Unified ionic and radical C-4 alkylation and arylation of pyridines.

C-H Functionalization of pyridines is an efficient strategy to access pyridine derivatives occurring in pharmaceuticals, agrochemicals, and materials. Nucleophilic additions to pyridiniums via both ionic and radical species have proven particularly useful. However, these reactions suffer from poor regioselectivity. By identifying an enzyme-mimic pocket-type urea activation reagent, we report a general platform for pyridine C-4 functionalization. Both ionic and radical nucleophiles can be incorporated to achieve the alkylation and arylation. Notably, the highly regioselective C-4 radical arylation is disclosed for the first time. The broad scope of nucleophiles and pyridines renders this platform applicable to the late-stage functionalization of drug-like molecules and the preparation of complex biologically important molecules.